Dry-AMD is characterized by degeneration of photoreceptors in the macula. Though macula makes up only a small part of the retina, it is much more sensitive to detail than peripheral retina. Dry AMD is the leading cause of new vision loss in ~15 million persons older than 65 years of age. Further, the degree of visual loss increases with ageing and this is a major concern for our demographic changes towards elderly population. Most of the current clinical treatments are primarily focused on slowing down the progression of the disease, as there is neither a cure that can stop the degeneration nor a therapy. We have developed an ambient-light activatable highly-photosensitive multi-characteristics opsin (MCO) to allow stimulation of photosensitized retinal ganglion cells for restoring vision in case of dry-AMD. However, clinical translation of such therapy (using optogenetic activation) for vision restoration is limited by the lack of approach for delivery of MCO- encoding genes into spatially-targeted regions of degenerated-retina (i.e. macula in dry-AMD). We have recently developed a continuous wave near-infrared (NIR) laser based method for efficient in-vivo delivery of exogenous material (including MCO-plasmids) into tissues. In this Nano-enhanced Optical Delivery (NOD?) method, we are utilizing the field enhancement by gold nanorods to transiently perforate cell membrane to deliver exogenous molecules to cells. Spatially-targeted in-situ delivery is achieved by shining the low-power continuous wave (cw) laser beam in targeted areas (e.g. geographic atrophy in AMD retina). Our preliminary results using NOD? method show that impermeable molecules (including opsin-plasmids) could be delivered into targeted cells using near-IR (NIR) continuous wave laser beam. Since the gold nanorods have very low cytotoxicity and have been widely used in various clinical trials, it is an ideal nanomaterial for clinical NOD. Compared with pulsed lasers, cw NIR (diode) lasers are compact, easy-to-use and therefore, have significant translational potential. The overall objective of this Phase I SBIR project is to demonstrate targeted in-vivo optical delivery of MCO to degenerated retinal regions in mice models of AMD using cw NIR laser beam in a safe manner. Towards this goal we have following aims: Towards this goal we have following aims: (i) Optimization of NOD for sensitizing RGCs with multi-characteristics opsin (MCO); and (ii) Assessment of long- term viability/retention and vision restoration in AMD mice model using electrophysiology. This proposal is a collaborative effort between NanoScope Technologies, and Drs. Mohanty and Kim's laboratories at University of Texas. Success of this proposal will lead to a new clinical approach for treating patients with dry AMD by intravitreal injection of gol nanorods and MCO, followed by NIR laser irradiation of targeted macular regions, thus photosensitizing those degenerated regions toward ambient day-light. Upon completion of the Phase I we envision a Phase II SBIR targeted at (i) optimizing the final product design and method, (ii) identifying AMD- population for treatment, (iii) submission of orphan drug/device license application to FDA, and (iv) providing core marketing material for commercializing the product and method.